This application for a Scientist Development Award for Clinicians is focused on the genetics of schizophrenia. The applicant is a psychiatrist who has conducted laboratory based as well as clinical research in schizophrenia and has received preliminary training in genetics. Support is requested in order to provide extensive training in molecular genetics and statistical techniques applied to psychiatric genetics. The training will be acquired by means of didactic courses and participation in ongoing and planned research projects. The applicant will thus gain expertise in conducting association studies using molecular genetic markers. During the first year, the applicant will develop a polymerase chain reaction (PCR) based assay for polymorphic alleles of the dopamine3 (D3) receptor gene. He will also analyze the relationship between outcome in schizophrenia and familial predisposition to unipolar affective disorder in a cohort which has already been recruited. These two projects will be supervised by Dr. S.R. Diehl and Dr. K.S. Kendler, respectively, at the Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia. During the rest of the award period, the applicant will conduct association studies at the University of Pittsburgh. Using molecular genetic and statistical expertise gained in year 01, he will initially investigate possible associations of schizophrenia (and sub-groups defined by age of onset) with alleles of two "candidate genes" which may be involved in the pathophysiology of schizophrenia: the genes encoding the dopamine2 (D2) and dopamine3 (D3) receptors. These studies will be conducted under the supervision of Dr. A. Chakravarti, Associate Professor of Human Genetics and Psychiatry, University of Pittsburgh, using stored DNA from patients (n=300) and matched unrelated controls. If an associations with the illness of its subgroup is found, it will be further investigated by recruiting more rigidly matched controls: unaffected relatives of the probands past the age for risk of schizophrenia. In addition to the training component, these studies may help elucidate the etiology of a common, devastating illness. The "association strategy" will complement the ongoing linkage studies in schizophrenia.